The purpose of these studies is to establish the basic developmental, and cellular events operating in the regulation of the genes coding for fetal gamma and adult Beta A and Beta C globins synthesized by sheep erythroid cells. The ultimate goal is to provide a biological rationale for either the therapeutic re-utilization of the human gamma gene or suppression of the switch from gamma to Beta globin production in disease conditions where defective Beta globin production results in severe anemia. Erythropoietin (ESF) causes a switch from Beta A to Beta C globin synthesis in adult bone marrow cells both in vivo and in vitro. In the fetus, the switch from gamma to Beta C synthesis by ESF may be initiated in vitro in cultures containing cells from mid- and late gestation fetal lambs. However, direct injection of ESF induces Beta C globin synthesis in vivo only just before birth.